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Protein

2-5A-dependent ribonuclease

Gene

Rnasel

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Endoribonuclease that functions in the interferon (IFN) antiviral response. In INF treated and virus infected cells, RNASEL probably mediates its antiviral effects through a combination of direct cleavage of single-stranded viral RNAs, inhibition of protein synthesis through the degradation of rRNA, induction of apoptosis, and induction of other antiviral genes. RNASEL mediated apoptosis is the result of a JNK-dependent stress-response pathway leading to cytochrome c release from mitochondria and caspase-dependent apoptosis. Therefore, activation of RNASEL could lead to elimination of virus infected cells under some circumstances. In the crosstalk between autophagy and apoptosis proposed to induce autophagy as an early stress response to small double-stranded RNA and at later stages of prolonged stress to activate caspase-dependent proteolytic cleavage of BECN1 to terminate autophagy and promote apoptosis. Might play a central role in the regulation of mRNA turnover (By similarity).By similarity1 Publication

Catalytic activityi

Cleaves 3' of UpNp dimers, with preference for UU and UA sequences, to sets of discrete products ranging from between 4 and 22 nucleotides in length.

Cofactori

Mn2+, Mg2+Note: Manganese or magnesium. Required for optimal RNA cleavage rates.

Enzyme regulationi

After binding to 2-5A (5'-phosphorylated 2',5'-linked oligoadenylates) the homodimerization and subsequent activation occurs. Inhibited by RNASEL inhibitor ABCE1/RLI, a cytoplasmic member of the ATP-binding cassette (ABC) transporter family (By similarity).By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri401 – 436C6-typeSequence analysisAdd BLAST36

GO - Molecular functioni

GO - Biological processi

  • defense response to virus Source: MGI
  • fat cell differentiation Source: MGI
  • mRNA processing Source: InterPro
  • negative regulation of viral genome replication Source: MGI
  • positive regulation of glucose import in response to insulin stimulus Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • regulation of mRNA stability Source: MGI
  • rRNA processing Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Endonuclease, Hydrolase, Nuclease

Keywords - Biological processi

Antiviral defense

Keywords - Ligandi

ATP-binding, Metal-binding, Nucleotide-binding, RNA-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-382556. ABC-family proteins mediated transport.

Names & Taxonomyi

Protein namesi
Recommended name:
2-5A-dependent ribonuclease (EC:3.1.26.-)
Short name:
2-5A-dependent RNase
Alternative name(s):
Ribonuclease 4
Ribonuclease L
Short name:
RNase L
Gene namesi
Name:Rnasel
Synonyms:Rns4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:1098272. Rnasel.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2687.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000670521 – 7352-5A-dependent ribonucleaseAdd BLAST735

Proteomic databases

EPDiQ05921.
MaxQBiQ05921.
PaxDbiQ05921.
PRIDEiQ05921.

PTM databases

iPTMnetiQ05921.
PhosphoSitePlusiQ05921.

Expressioni

Tissue specificityi

Expressed in spleen, thymus, lung, testis, kidney, liver and heart.

Inductioni

By interferons. Virus replication in higher vertebrates is restrained by IFNs that cause cells to transcribe genes encoding antiviral proteins, such as 2'-5' oligoadenylate synthetases (OASs). oligoadenylate synthetase is stimulated by dsRNA to produce 5'-phosphorylated, 2'-5'-linked oligoadenylates (2-5A), whose function is to activate RNASEL.

Gene expression databases

BgeeiENSMUSG00000066800.
ExpressionAtlasiQ05921. baseline and differential.
GenevisibleiQ05921. MM.

Interactioni

Subunit structurei

Monomer (inactive form) or homodimer. Interacts with ABCE1; this interaction inhibits the RNASEL (By similarity).By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000083385.

Chemistry databases

BindingDBiQ05921.

Structurei

3D structure databases

ProteinModelPortaliQ05921.
SMRiQ05921.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati24 – 53ANK 1Add BLAST30
Repeati58 – 87ANK 2Add BLAST30
Repeati91 – 120ANK 3Add BLAST30
Repeati124 – 153ANK 4Add BLAST30
Repeati167 – 197ANK 5Add BLAST31
Repeati201 – 234ANK 6Add BLAST34
Repeati238 – 268ANK 7Add BLAST31
Repeati272 – 301ANK 8Add BLAST30
Repeati303 – 328ANK 9Add BLAST26
Domaini364 – 584Protein kinasePROSITE-ProRule annotationAdd BLAST221
Domaini587 – 722KENPROSITE-ProRule annotationAdd BLAST136

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni229 – 2422-5A binding (P-loop) 1Add BLAST14
Regioni253 – 2752-5A binding (P-loop) 2Add BLAST23

Domaini

The nine ankyrin repeats also called 2-5A sensor constitute the N-terminus 2-5A binding domain.
The protein kinase domain is predicted to be catalytically inactive. It allows the homodimerization.
The ribonuclease domain is located in the C-terminus. A single active nuclease domain in a dimer is sufficient for ribonuclease activity.

Sequence similaritiesi

Belongs to the protein kinase superfamily.Curated
Contains 9 ANK repeats.PROSITE-ProRule annotation
Contains 1 KEN domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri401 – 436C6-typeSequence analysisAdd BLAST36

Keywords - Domaini

ANK repeat, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1027. Eukaryota.
KOG4177. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00840000129724.
HOGENOMiHOG000276879.
HOVERGENiHBG012673.
InParanoidiQ05921.
KOiK01165.
OMAiDCGDLVM.
OrthoDBiEOG091G03H3.
PhylomeDBiQ05921.
TreeFamiTF344032.

Family and domain databases

Gene3Di1.25.40.20. 3 hits.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR010513. KEN_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR018997. PUB_domain.
[Graphical view]
PfamiPF12796. Ank_2. 2 hits.
PF13606. Ank_3. 1 hit.
PF00069. Pkinase. 1 hit.
PF06479. Ribonuc_2-5A. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
SMARTiSM00248. ANK. 8 hits.
SM00580. PUG. 1 hit.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 7 hits.
PS51392. KEN. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q05921-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
METPDYNTPQ GGTPSAGSQR TVVEDDSSLI KAVQKGDVVR VQQLLEKGAD
60 70 80 90 100
ANACEDTWGW TPLHNAVQAG RVDIVNLLLS HGADPHRRKK NGATPFIIAG
110 120 130 140 150
IQGDVKLLEI LLSCGADVNE CDENGFTAFM EAAERGNAEA LRFLFAKGAN
160 170 180 190 200
VNLRRQTTKD KRRLKQGGAT ALMSAAEKGH LEVLRILLND MKAEVDARDN
210 220 230 240 250
MGRNALIRTL LNWDCENVEE ITSILIQHGA DVNVRGERGK TPLIAAVERK
260 270 280 290 300
HTGLVQMLLS REGINIDARD NEGKTALLIA VDKQLKEIVQ LLLEKGADKC
310 320 330 340 350
DDLVWIARRN HDYHLVKLLL PYVANPDTDP PAGDWSPHSS RWGTALKSLH
360 370 380 390 400
SMTRPMIGKL KIFIHDDYKI AGTSEGAVYL GIYDNREVAV KVFRENSPRG
410 420 430 440 450
CKEVSCLRDC GDHSNLVAFY GREDDKGCLY VCVSLCEWTL EEFLRLPREE
460 470 480 490 500
PVENGEDKFA HSILLSIFEG VQKLHLHGYS HQDLQPQNIL IDSKKAVRLA
510 520 530 540 550
DFDQSIRWMG ESQMVRRDLE DLGRLVLYVV MKGEIPFETL KTQNDEVLLT
560 570 580 590 600
MSPDEETKDL IHCLFSPGEN VKNCLVDLLG HPFFWTWENR YRTLRNVGNE
610 620 630 640 650
SDIKVRKCKS DLLRLLQHQT LEPPRSFDQW TSKIDKNVMD EMNHFYEKRK
660 670 680 690 700
KNPYQDTVGD LLKFIRNIGE HINEEKKRGM KEILGDPSRY FQETFPDLVI
710 720 730
YIYKKLKETE YRKHFPQPPP RLSVPEAVGP GGIQS
Length:735
Mass (Da):83,275
Last modified:February 11, 2002 - v2
Checksum:iB6632F4A5B50F711
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF281045 mRNA. Translation: AAG33708.1.
L10382 Genomic DNA. Translation: AAA37117.1.
CCDSiCCDS15377.1.
PIRiB45771.
RefSeqiNP_036012.1. NM_011882.2.
XP_006529590.1. XM_006529527.3.
XP_006529591.1. XM_006529528.3.
XP_006529593.1. XM_006529530.2.
XP_011246295.1. XM_011247993.2.
UniGeneiMm.259254.

Genome annotation databases

EnsembliENSMUST00000086209; ENSMUSP00000083385; ENSMUSG00000066800.
GeneIDi24014.
KEGGimmu:24014.
UCSCiuc007daf.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF281045 mRNA. Translation: AAG33708.1.
L10382 Genomic DNA. Translation: AAA37117.1.
CCDSiCCDS15377.1.
PIRiB45771.
RefSeqiNP_036012.1. NM_011882.2.
XP_006529590.1. XM_006529527.3.
XP_006529591.1. XM_006529528.3.
XP_006529593.1. XM_006529530.2.
XP_011246295.1. XM_011247993.2.
UniGeneiMm.259254.

3D structure databases

ProteinModelPortaliQ05921.
SMRiQ05921.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000083385.

Chemistry databases

BindingDBiQ05921.
ChEMBLiCHEMBL2687.

PTM databases

iPTMnetiQ05921.
PhosphoSitePlusiQ05921.

Proteomic databases

EPDiQ05921.
MaxQBiQ05921.
PaxDbiQ05921.
PRIDEiQ05921.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000086209; ENSMUSP00000083385; ENSMUSG00000066800.
GeneIDi24014.
KEGGimmu:24014.
UCSCiuc007daf.1. mouse.

Organism-specific databases

CTDi6041.
MGIiMGI:1098272. Rnasel.

Phylogenomic databases

eggNOGiKOG1027. Eukaryota.
KOG4177. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00840000129724.
HOGENOMiHOG000276879.
HOVERGENiHBG012673.
InParanoidiQ05921.
KOiK01165.
OMAiDCGDLVM.
OrthoDBiEOG091G03H3.
PhylomeDBiQ05921.
TreeFamiTF344032.

Enzyme and pathway databases

ReactomeiR-MMU-382556. ABC-family proteins mediated transport.

Miscellaneous databases

PROiQ05921.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000066800.
ExpressionAtlasiQ05921. baseline and differential.
GenevisibleiQ05921. MM.

Family and domain databases

Gene3Di1.25.40.20. 3 hits.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR010513. KEN_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR018997. PUB_domain.
[Graphical view]
PfamiPF12796. Ank_2. 2 hits.
PF13606. Ank_3. 1 hit.
PF00069. Pkinase. 1 hit.
PF06479. Ribonuc_2-5A. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
SMARTiSM00248. ANK. 8 hits.
SM00580. PUG. 1 hit.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 7 hits.
PS51392. KEN. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRN5A_MOUSE
AccessioniPrimary (citable) accession number: Q05921
Secondary accession number(s): Q9ERU7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: February 11, 2002
Last modified: November 2, 2016
This is version 146 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.